The predictive role of flow cytometry-derived tumor potential doubling time (Tpot) in radiotherapy: open questions and future perspectives.

Antognoni, Paolo; Nha, Nha Terry; Richetti, A.; Luraghi, Roberto; Tordiglione, M; Danova, Marco

doi:10.3892/ijo.12.2.245

Cited by 6 publications

(7 citation statements)

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“…However, the proposed method may underestimate GF in diploid tumours, if procedures to separate normal cells from tumour cells are not used. The possible solutions to tackle this problem have been summarized by Antognoni P et al [2] and are mainly based on using cytokeratin markers to separate epithelial tumour cells from intratumoural inflammatory cells and fibroblasts. In addition, it is recommended to present cell kinetic data from diploid and aneuploid tumours separately [17].…”

Section: Discussionmentioning

confidence: 99%

“…T pot is defined as the time to double the number of proliferating cells in the absence of cell loss [1]. This derived cell kinetic parameter has been postulated to be a predictor of a tumour's proliferative capability and has been widely studied in clinic in an attempt to find its prognostic significance and the potential value in predicting treatment outcome [2]. However, more recent evidence has not confirmed the existence of association between T pot and disease outcome measures, whereas information on clinical significance of LI and T S remains ambiguous [3-5].…”

Section: Introductionmentioning

confidence: 99%

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A method to estimate cell cycle time and growth fraction using bromodeoxyuridine-flow cytometry data from a single sample

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A method to estimate cell cycle time and growth fraction using bromodeoxyuridine-flow cytometry data from a single sample

et al. 2005

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“…The procedure is relatively simple: Compute c from equation [5] using the values of and derived from f lu (t), f ld (t), and RM(t). Then apply equations [1], [2], and [3] to obtain T G2ϩM , T S , and T pot .…”

Section: Discussionmentioning

confidence: 99%

“…The calculation of the proliferative parameters of cell populations, particularly the potential doubling time (T pot ), and the durations of DNA synthesis (T S ) and the G2ϩM phases (T G2ϩM ) of the cell cycle is useful in clinical studies (2). These calculations provide insight into cell cycle regulation (14) and the effects of drugs or radiation on cell progression (27,28,29).…”

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confidence: 99%

Simultaneous estimation ofTG2+M,TS, andTpot using single sample dynamic tumor data from bivariate DNA-thymidine analogue cytometry

et al. 2000

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Background Estimating the duration of S phase (TS ) and the potential doubling time (Tpot ) from a single time measurement of the movement of cells using bivariate cytometry is common. However, these estimates require an assumption of the duration of G2 + M (TG2+M ). Inspection of the measured dynamic quantities, relative movement [RM(t)], fractions of labeled divided and undivided cells (flu(t) and fld(t)) suggests that TG2+M, TS, and Tpot can be determined simultaneously. Methods An equation connecting the growth of the cell population, time, and the dynamic quantities was determined. The equation cannot be solved analytically, but accurate approximations can be used to find Tpot. From this result, the value of TG2+M can be determined from fld(t), and TS can be determined from RM(t). Results Kinetic parameters obtained from single time estimates using the new method compared to those obtained from the analysis of multiple time‐point measurements of MCa‐K and MCa‐4 murine tumors are shown to be in close agreement. Moreover, estimates of TG2+M in MCa‐4 tumors, treated with paclitaxel, provide extra information on the changes in TG2+M. When applied to the rat R3327‐G prostate tumor model following androgen ablation, a correlation analysis of the Tpot values obtained by the new and previous single time‐point methods demonstrates that the rank order from shortest to longest Tpot values are largely preserved. Conclusions The new procedure makes direct estimation of TG2+M possible from single time‐dynamic measurements. The results from previous studies on TS and Tpot are largely unchanged, but extra information is now available. Cytometry 41:1–8, 2000 © 2000 Wiley‐Liss, Inc.

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“…There are many reasons why SF2 will not predict tumor cure for all patients. Any effects that are due to the tumor environment such as hypoxia (32), angiogenesis (33), tumor immunity (34), or cell cycle distribution (35) will not be predicted by standard SF2 studies. Interestingly, cell cycle effect can be predicted by DNA-EBC analysis.…”

Section: Discussionmentioning

confidence: 99%

Predicting Radiosensitivity Using DNA End-Binding Complex Analysis

Ismail¹,

Puppi²,

Prithivirajsingh³

et al. 2004

Clinical Cancer Research

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Previous reports have suggested that measuring radiosensitivity of normal and tumor cells would have significant clinical relevance for the practice of radiation oncology. We hypothesized that radiosensitivity might be predicted by analyzing DNA end-binding complexes (DNA-EBCs), which form at DNA double-strand breaks, the most important cytotoxic lesion caused by radiation. To test this hypothesis, the DNA-EBC pattern of 21 primary human fibroblast cultures and 15 tumor cell lines were studied. DNA-EBC patterns were determined using a modified electrophoretic mobility shift assay and were correlated with radiosensitivity, as measured by SF2. DNA-EBC analysis identified a rapidly migrating ATM-containing band (identified as "band-A") of which the density correlated with SF2 (0.02 < SF2 < 0.41) in primary fibroblasts (r 2 ‫؍‬ 0.77). The DNA-EBC pattern of peripheral blood lymphocytes was identical to that of fibroblasts. In addition, band-A density correlated with SF2 (0.35 < SF2 < 0.80) in 15 human tumor cell lines (r 2 ‫؍‬ 0.91). Densitometry of other bands, or total DNA-EBC binding, correlated more poorly with SF2 (r 2 < 0.45). These data indicate that DNA-EBC analysis may be a practical, clinically relevant predictor of tumor and primary cell radiosensitivity.

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The predictive role of flow cytometry-derived tumor potential doubling time (Tpot) in radiotherapy: open questions and future perspectives.

Cited by 6 publications

References 0 publications

A method to estimate cell cycle time and growth fraction using bromodeoxyuridine-flow cytometry data from a single sample

A method to estimate cell cycle time and growth fraction using bromodeoxyuridine-flow cytometry data from a single sample

Simultaneous estimation ofTG2+M,TS, andTpot using single sample dynamic tumor data from bivariate DNA-thymidine analogue cytometry

Predicting Radiosensitivity Using DNA End-Binding Complex Analysis

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